Process for the production of 4-(2-hy-droxyethoxy) benzoic acid lower alkyl esters of high purity

ABSTRACT

A PROCESS FOR PRODUCING 4-(2-HYDROXYETHOXY) BENZOIC ACID LOWER ALKYL ESTERS WHICH COMPRISES DISSOLVING OR SUSPENDING A MIXTURE OF AN ALKALI METAL SALT OF A 4-HYDROXY BENZOIC ACID LOWER ALKYL ESTER, WHERE THE LOWER ALKYL IS OF NOT MORE THAN 6 CARBON ATOMS, AND A 4-HYDROXY BENZOIC ACID LOWER ALKYL ESTER, IN AN INERT ORGANIC SOLVENT, AND CONTACTING THE RESULTING SOLUTION OR SUSPENSION WITH ETHYLENE OXIDE.

United States Patent Ofice 3,734,947 Patented May 22, 1973 PROCESS FOR THE PRODUCTION OF 4-(2-HY- DROXYETHOXY) BENZOIC ACID LOWER ALKYL ESTERS OF HIGH PURITY Ryuzo Ueno and Motomu Kashihara, Nishinomiya, Japan, assignors to Kabushiki Kaisha Ueno Seiyaku Oyo Kenkyujo, Osaka, Japan No Drawing. Filed July 23, 1970, Ser. No. 57,768 Int. Cl. C07c 69/78 U.S. Cl. 260473 R 3 Claims ABSTRACT OF THE DISCLOSURE A process for producing 4-(2-hydroxyethoxy) benzoic acid lower alkyl esters which comprises dissolving or suspending a mixture of an alkali metal salt of a 4-hydroxy benzoic acid lower alkyl ester, Where the lower alkyl is of not more than 6 carbon atoms, and a 4-hydroxy benzoic acid lower alkyl ester, in an inert organic solvent, and contacting the resulting solution or suspension with ethylene oxide.

This invention relates to a process for the production of 4-(2-hydroxyethoxy)benzoic acid lower alkyl esters (lower alkyl of not more than C of high purity.

The 4-(2-hydroxyethoxy) benzoic acid esters, which are used as the starting material for the production of such macromolecular compounds as synthetic fibers and films, are usually prepared by the esterification of 4-(2- hydroxyethoxy) benzoic acid [Japanese patent publication No. 3,717/1962; Chemical Abstracts 58, 8984 (1963)]. This method however has the drawbacks that a great quantity of inorganic catalysts are used, with the consequence that unless these salts are completely removed, an undesirable polymerization reaction is set up during the distillation of the product to cause a pronounced reduction in the yield of the product, or that the purity of the product suffers as a result of the minute quantity of 2-(2-hydroxyethoxy) benzoic acid that is contained in the starting car-boxylic acid. As another method of hydroxyethylating the 4-hydroxy benzoic acid esters, one is known wherein the 4-hydroxy benzoic acid ester is reacted with ethylenechlorohydrin in an aqueous solution in the presence of an alkali metal hydroxide (German Pat. No. 412,699; Chemisches Zentralblat 1925 II, 613), but there is a tendency to hydrolysis of the starting 4-hydroxy benzoic acid ester or the intended 4- (Z-hydroxyethoxy) benzoic acid ester taking place and the yield of the intended product is only ca. 50%. Aside from these, methods of obtaining 4-(2-hydroxyethoxy) benzoic acid by reacting the 4-hydroxy benzoic acid ester with ethylene oxide while maintaining the reactants in a molten state or adding a solvent such as alcohols in such a small quantity as will bring about a rise in the boiling point of the reactants, and using as catalyst either an alkali metal, alkali metal hydroxide or a halogen salt of a strong alkaline base are known [Japanese patent publication No. 4,124/ 1962; Chemical Abstracts 59, 2727 (1963); Japanese patent publication No. 4,521/1962; Chemical Abstracts 58, 10131 (1963)]. However, when these methods were investigated in detail, it was confirmed that the reaction with ethylene oxide hardly took place when the halogen salts of strong alkaline bases (e.g. KBr, NaBr, NaCl, (CH NCl, etc.) were used, with the consequence that the intended product could only be obtained at a very low yield; that in the case where a solvent is not used, for the reason that the melting point, say, of methyl 4-hydroxy benzoate is 127128 C., the reaction temperature must be raised to above this temperature, with the consequence that self-condensation of the product 4*(2-hydroxyethoxy) benzoate takes place in the presence of alkali metals or alkali metal hydroxides to result in a yield of 80% at most; that, on the other hand, when the alcohols are used as the solvent, the alcohols react with ethylene oxide to form glycol ethers and, as a result, practically no reaction takes place with the 4-hydroxy benzoic acid ester.

As a result of our researches with a view to overcoming the shortcomings of the conventional methods and thus to provide for the obtainment of the 4-(2-hydroxyethoxy) benzoic acid lower alkyl esters of high purity at low cost, we arrived at the present invention.

We made a detailed inquiry into the properties of the mixture of the alkali metal salts of 4-hydroxy benzoic acid lower alkyl esters and 4-hydroxy benzoic acid lower alkyl esters and considered the use also of an inert solvent. It was found by our researches that while the alkali metal salts of 4-hydroxy benzoic acid lower alkyl esters are readily soluble in water but usually diflicultly soluble in organic solvents the mixture thereof with 4-hydroxy benzoic acid lower alkyl esters becomes liquid at a relatively low temperature as a result of second order transition. For example, a mixture of the sodium salt of methyl 4-hydroxy benzoate and methyl 4-hydroxy benzoate becomes liquid in the neighborhood of 100 C., and this mixture easily dissolves or is readily suspended in solvents. Thus, it was found that if a mixture of an alkali metal salt of a 4-hydroxy benzoic acid lower alkyl ester and a 4-hydroxy benzoic acid lower alkyl ester is reacted with ethylene oxide after being dissolved or suspended in a solvent which is inert to ethylene oxide, a first order reaction in the alkali metal salt of a 4-hydroxy benzoic acid lower alkyl ester and a first order reaction in ethylene oxide take place to result, when combined, a second order reaction in. As a result, it becomes possible to complete the reaction in a short period of time at a temperature which does not induce undesirable side reactions. Hence, a 4-(2-hydroxyethoxy) benzoic acid lower alkyl ester of high purity can be obtained at a high yield of above 95%. Needless to say, the unreacted 4-hydroxy benzoic acid lower alkyl ester and its alkali metal salt can be recovered with practically no loss.

The present invention is directed to a process for the production of 4-(2-hydroxyethoxy) benzoic acid lower alkyl esters of high purity which comprises dissolving or suspending a mixture of an alkali metal salt of a 4-hydroxy benzoic acid lower alkyl ester (where the lower alkyl is C or less) and a 4-hydroxy benzoic acid lower alkyl ester in an inert solvent and contacting this solution or suspension with ethylene oxide to effect the reaction of the reactants.

Since a 4-hydroxy benzoic acid lower alkyl ester is used according to the invention, there is practically no possibility of such impurities as 2-(2-hydroxyethoxy) benzoic acid esters or inorganic impurities which set up undesirable polymerization reaction during the distillation step of the intended product being present. Hence, a 4-(2- hydroxyethoxy) benzoic acid lower alkyl ester of high purity can be readily obtained according to the present invention. And hardly any side reactions take place, since no use is made of such strong alkalis as alkali metal hydroxides. Again, the commercial practice of the invention is simplified, since hazardous materials such as the alkali metals are not used. Moreover, since the reaction can be carried out with a solution or a good suspension and it proceeds promptly, it can be operated continuously. Thus, it is seemed that the invention process possesses countless advantages.

In practicing the present invention, the reaction, as hereinbefore noted, is carried out by adding an inert solvent to a mixture of an alkali metal salt of a 4-hydroxy benzoic acid lower alkyl ester (lower alkyl of below C and a 4-hydroxy benzoic acid lower alkyl ester and then blowing in ethylene oxide while heating the mixture with stirring. As the inert solvent, useable are, for example, the ketones such as methyl ethyl ketone and methyl isobutyl ketone, the aromatic hydrocarbons such as benzene and toluene, the hydrocarbons such as the petroleum aliphatic hydrocarbons, the ethers such as isopropyl ether, isobutyl ether and phenyl ether, and especially the ethers of above 6 carbon atoms. The reactions can be carried out if the molar ratio of the alkali metal salt of 4-hydroxy benzoic acid lower alkyl ester to the 4-hydroxy benzoic acid lower alkyl ester is less than 1021, but from the economical standpoint a molar ratio of 1:1-1:50, and especially 1:2- 1:20, is preferred. A reaction temperature of 50-120 C., and preferably 70-100 C., is used.

As the starting 4-hydroxy benzoic acid lower alkyl ester, useable are any of such as the methyl, ethyl, nor ispropyl and n-, iso-, sec-, or tert-butyl esters. On the other hand, as the alkali metal salts thereof, useable are either the lithium, sodium or potassium salts; but from the standpoint of commercial operations the sodium and potassium salts are preferred.

While the mixture of the alkali metal salt of a 4-hydroxy benzoic acid lower alkyl ester and a 4-hydroxy benzoic acid lower alkyl ester can be dissolved or suspended in an inert solvent at concentrations whose permissible range is broad, the mixture is usually dissolved or suspended in the inert organic solvent preferably such that its concentration becomes to 80%, and particularly to 70%.

The reaction can be carried out continuously or batchwise, employing a gas-liquid contact apparatus such, for example, as a packed, porous or perforated column. While normal pressure will sufiice for the reaction pressure, it is, of course, also possible to carry out the reaction under conditions of application of some pressure. Again, it is usually desirable to continuously agitate the reaction system for ensuring the uniform dispersion of the foregoing starting mixture in the inert organic solvent. The amount of ethylene oxide to be blown into the reaction system will suffice if it is an amount equimolar to that of the 4-hydroxy benzoic acid lower alkyl ester contained in the starting mixture. Although the reaction time will vary depending upon the temperature, generally speaking, a period of time ranging between minutes and 10 hours is employed, the ethylene oxide in the amount hereinbefore indicated being blown in during this period. In carrying out this operation, the reactor can be equipped with a reflux condenser and thus prevent the unreacted ethylene oxide from being carried off to the outside of the system.

The reaction can be carried out either in a single stage or a plurality of stages. For example, the mixture of the alkali meal salt of a 4-hydroxy benzoic acid lower alkyl ester and a 4-hydroxy benzoic acid lower alkyl ester can be first reacted with ethylene oxide, then after the aforementioned reaction time has elapsed, an additional amount of the 4-hydroxy benzoic acid lower alkyl ester, along with an additional quantity of the inert solvent, if necessary, can be introduced into the reaction system, and thereafter the reaction can be continued by further flowing in of ethylene oxide.

After removing the unreacted alkali metal salt of 4- hydroxy benzoic acid lower alkyl ester from the reaction product by extraction with water or a dilute aqueous alkali solution and the unreacted 4-hydroxy benzoic acid lower alkyl ester by extraction with a dilute aqueous alkali solution or a solvent such as isopropyl ether, the reaction product is submitted to vacuum distillation and other operations to thereby obtain the intended 4-(2-hydroxyethoxy) benzoic acid lower alkyl ester of high purity.

EXAMPLE I A reactor equipped with a stirrer and an ice-cooled reflux condenser was charged with 17.4 grams of a sodium salt of methyl 4-hydroxy benzoate, 45.6 grams of methyl 4-hydroxy benzoate and 63 ml. of methyl isobutyl ketone,

and the etherification reaction was carried out by blowing in 13.2 grams of ethylene oxide at 85 C. during a 2- hour period. After completion of the reaction, the reaction mixture was extracted with ml. of 5% sodium hydroxide solution to remove the unreacted sodium salt of methyl 4-hydroxy benzoate and methyl 4-hydroxy benzoate, washed thoroughly with water, followed by distilling off of the methyl isobutyl ketone, and thereafter submission of the residue to vacuum distillation, whereupon was obtained methyl 4-(2-hydroxyethoxy) benzoate of high purity in an amount of 56.3 grams (yield 95.8% on the basis of the methyl 4-hydroxy benzoate). The sodium hydroxide solution layer was neutralized with hydrochloric acid, and 16.6 grams of methyl 4-hydroxy benzoate were recovered.

EXAMPLE II Example I was repeated except that 8.7 grams of a sodium salt of methyl 4-hydroxy benzoate, 45.6 grams of methyl 4-hydroxy benzoate and 54.3 ml. of methyl isobutyl ketone were used, whereupon was obtained methyl 4-(2-hydroxyethoxy) benzoate of high purity in an amount of 56.2 grams (yield 95.2%). The recovered methyl 4-hydroxy benzoate amounted to 9.1 grams.

EXAMPLE III A reactor equipped with a stirrer and an ice-cooled reflux condenser was charged with 20.4 grams of a potassium salt of ethyl 4-hydroxy benzoate, 49.8 grams of ethyl 4-hydroxy benzoate and ml. of toluene, and the etherification reaction was carried out by blowing in 13.2 grams of ethylene oxide at 80-85 C. during a 3-hour period. After completion of the reaction, the unreacted potassium salt of ethyl 4-hydroxy benzoate was removed by extraction with water, then the methyl isobutyl ketone was distilled off, and 50 ml. of isopropyl ether were added to the reaction product and stirred for 30 minutes. When the crystals obtained after separation of the contents by filtration were submitted to vacuum distillation, ethyl 4- (Z-hydroxyethoxy) benzoate of high purity was obtained in an amount of 60.5 grams (yield 96.1% based on the ethyl 4-hydroxy benzoate). Twenty grams of the potassium salt of ethyl 4-hydroxy benzoate and 1.5 grams of the ethyl 4-hydroxy benzoate were recovered from the aqueous and isopropyl ether layers, respectively.

EXAMPLE IV A reactor equipped with a stirrer and an ice-cooled reflux condenser was charged with 29 grams of a sodium salt of n-butyl 4-hydroxy benzoate, 64.8 grams n-butyl 4-hydroxy benzoate and 67.7 ml. of isopropyl ether, following which 19.8 grams of ethylene oxide were blown into the reactor at 73-76" C. during a 5-hour period. After completion of the reaction, the unreacted sodium salt of n-butyl 4-hydroxy benzoate was removed by extraction with water, followed by recovering 30 ml. of the isopropyl ether and cooling of the reaction mixture. When the crystals obtained after separation of the contents by filtration were submitted to vacuum distillation, n-butyl 4-(2-hydroxyethoxy) benzoate was obtained in an amount of 73.9 grams (yield of 92.9% based on the n-butyl 4-hydroxy benzoate) 28.7 grams of the sodium salt of n-butyl 4-hydroxy benzoate and 3.3 grams of n-butyl 4-hydr0xy benzoate were recovered from the aqueous and the isopropyl ether layers, respectively.

We claim:

1. A process for producing 4-(2-hydroxyethoxy) benzoic acid lower alkyl esters which comprises dissolving or suspending a mixture of an alkali metal salt of a 4-hydroxy benzoic acid lower alkyl ester where the lower alkyl is of not more than 6 carbon atoms, and a 4-hydroxy benzoic acid lower alkyl ester wherein the molar ratio of the alkali metal salt of the 4-hydroxy benzoic acid lower alkyl ester to the 4-hydroxy benzoic acid lower alkyl ester in said mixture ranges from 1:1 to 1:20, in an inert organic solvent selected from the group consisting of ketones, aromatic and aliphatic petroleum hydrocar- References Cited bons and ethers and contacting the resulting solution UNITED STATES PATENTS or suspension with ethylene oxide at a temperature of from 70 to 100 (3., whereby the finally produced 4-(2- 2,154,598 4/1939 Bass et a1 260473 R X hydroxyethoxy) benzoic acid lower alkyl ester has the 5 FOREIGN PATENTS same alkyl group in the ester moiety as the alkali metal 8 36,544 6/1960 Great Britain 260473 R salt 4 hydroxy benzolc acid lower alkyl ester reactant. 4,124 1962 Japan 26O 473 R 2. The process according to claim 1 wherein said solution or suspension is contacted with ethylene oxide at a LORRAINE A WEINBERGER Primal, Examiner temperature ranging between 50 C and 120 C. 10 y 3. A process according to claim 1, where the reaction TERAPANE, Assistant mlncr time ranges from thirty minutes to ten hours. 

